Abstract
Background
The duodenum plays a role in the mechanism of type 2 diabetes remission after bariatric
surgery. Roux-en-Y gastric bypass (RYGB) may change gene expression in the duodenum
and metabolism. Long noncoding RNAs (lncRNAs) constitute a novel class of RNAs that
regulate gene expression. Little is known about how duodenal lncRNAs respond to RYGB.
Logically, studies on the changes of duodenal lncRNAs potentially can lead to an understanding
of the mechanisms of bariatric surgery, as well as discovery of antidiabetic drug
targets and biomarkers predicting postoperative outcome.
Objectives
To investigate the expression signature of duodenal lncRNAs associated with glycemic
improvement by duodenal-jejunal bypass (DJB), a component of RYGB, on a genome-wide
scale in high-fat diet–induced diabetic mice.
Setting
University medical center.
Methods
High fat diet–induced diabetic mice were randomized into 2 groups receiving either
the DJB or a sham procedure. Microarray was applied to screen the differentially expressed
lncRNAs and messenger RNAs (mRNAs) in the duodenum between the DJB and sham groups,
and the result was validated by quantitative real-time polymerase chain reaction in
another cohort of animals. Gene ontology (GO) and Kyoto Encyclopedia of Genes and
Genomes (KEGG) pathway analyses were performed to predict the potential lncRNA functions.
Based on Pearson correlation analysis, the lncRNA-mRNA and lncRNA-transcription factor
(TF) interaction networks were constructed to identify and rank core regulatory lncRNAs
and transcription factors.
Results
A total of 301 lncRNAs, including 232 that were upregulated and 69 downregulated (fold
change≥2.0), were differentially expressed in the duodenum between the DJB and sham
groups. GO enrichment indicated that these lncRNA-coexpressed mRNAs were correlated
with biological processes including cell proliferation, digestion, and catabolic and
biosynthetic processes. KEGG pathway analysis revealed that in addition to the digestion
and absorption signaling pathways, pancreatic secretion– and inflammatory process–related
signaling pathways were mostly enriched in the DJB group. In addition, the lncRNA-mRNA
interaction network combined with GO and KEGG pathway analysis suggested that as a
top-ranked gene, NONMMUG021726 may play an important role in the mechanism of type
2 diabetes remission after DJB.
Conclusion
DJB leads to drastic changes in lncRNA and mRNA expressions in the duodenum. The majority
of top-ranked lncRNAs and mRNAs have roles in pancreatic secretion and inflammatory
processes, implying that bypass of the duodenum may initiate insulin secretion and
attenuate inflammation. In addition, modulators of such lncRNAs, most likely NONMMUG021726,
have potential to become therapeutic targets or biomarkers for prediction of the outcomes
of bariatric surgery.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Surgery for Obesity and Related DiseasesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Global estimates of diabetes prevalence for 2013 and projections for 2035.Diabetes Res Clin Pract. 2014; 103: 137-149
- Are obesity-related insulin resistance and type 2 diabetes autoimmune diseases?.Diabetes. 2015; 64: 1886-1897
- LIGHT/TNFSF14 is increased in patients with type 2 diabetes mellitus and promotes islet cell dysfunction and endothelial cell inflammation in vitro.Diabetologia. 2016; 59: 2134-2144
- DPP4 in diabetes.Front Immunol. 2015; 6: 386
- Efficacy and safety of once-weekly glucagon-like peptide 1 receptor agonists for the management of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.Diabetes Obes Metab. 2015; 17: 1065-1074
- Emerging opportunities for the treatment of metabolic diseases: Glucagon-like peptide-1 based multi-agonists.Mol Cell Endocrinol. 2015; 418: 42-54
- Canagliflozin for the treatment of type 2 diabetes.Drugs Today (Barc). 2013; 49: 363-376
- Standards of medical care in diabetes 2015.Diabetes Care. 2015; 38: S1-S90
- A nationwide safety analysis of bariatric surgery in nonseverely obese patients with type 2 diabetes.Surg Obes Relat Dis. 2016; 12: 1163-1170
- Incretins or anti-incretins? A new model for the “entero-pancreatic axis.”.Horm Metab Res. 2015; 47: 84-87
- Effects of endogenous GLP-1 and GIP on glucose tolerance after Roux-en-Y gastric bypass surgery.Am J Physiol Endocrinol Metab. 2016; 310: 505-514
- Exaggerated release and preserved insulinotropic action of glucagon-like peptide-1 underlie insulin hypersecretion in glucose-tolerant individuals after Roux-en-Y gastric bypass.Diabetologia. 2013; 56: 2679-2687
- Peptide YY and glucagon-like peptide-1 contribute to decreased food intake after Roux-en-Y gastric bypass surgery.Int J Obes (Lond). 2016; 40: 1699-1706
- Long-term changes in leptin, chemerin and ghrelin levels following different bariatric surgery procedures: Roux-en-Y gastric bypass and sleeve gastrectomy.Obes Surg. 2013; 23: 1790-1798
- Duodenal-jejunal bypass for the treatment of type 2 diabetes in patients with body mass index of 22-34 kg/m2: a report of 2 cases.Surg Obes Relat Dis. 2007; 3: 195-197
- Effects of duodenal-jejunal bypass liner (EndoBarrier®) on gastric emptying in obese and type 2 diabetic patients.Obes Surg. 2015; 25: 1618-1625
- Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes: 6-month interim analysis from the first-in-human proof-of-concept study.Diabetes Care. 2016; 39: 2254-2261
Jurets A, Itariu BK, Keindl M, et al. Upregulated TNF expression 1 year after bariatric surgery reflects a cachexia-like state in subcutaneous adipose tissue. Obes Surg. Epub 2016 Nov 29
- Structure and function of long noncoding RNAs in epigenetic regulation.Nat Struct Mol Biol. 2013; 20: 300-307
- Long noncoding RNAs and human disease.Trends Cell Biol. 2011; 21: 354-361
- Long noncoding RNAs: functional surprises from the RNA world.Genes Dev. 2009; 23: 1494-1504
- Long noncoding RNA HOTAIR reprograms chromatin state to promote cancer metastasis.Nature. 2010; 464: 1071-1076
- lincRNAs act in the circuitry controlling pluripotency and differentiation.Nature. 2011; 477: 295-300
- Gastric volume reduction is essential for the remission of type 2 diabetes mellitus after bariatric surgery in nonobese rats.Surg Obes Relat Dis. 2016; 12: 1569-1576
- Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease.Ann Surg. 2004; 239: 1-11
- Establishment of duodenojejunal bypass surgery in mice: a model designed for diabetic research.Microsurgery. 2008; 28: 197-202
Goh YM, Toumi Z, Date RS. Surgical cure for type 2 diabetes by foregut or hindgut operations: a myth or reality? A systematic review. Surg Endosc. Epub 2016 May 18
- Effect of duodenal-jejunal bypass surgery on glycemic control in type 2 diabetes: a randomized controlled trial.Obesity (Silver Spring). 2015; 23: 1973-1979
- Weight loss and metabolic improvement in morbidly obese subjects implanted for 1 year with an endoscopic duodenal-jejunal bypass liner.Ann Surg. 2012; 255: 1080-1085
- Biliopancreatic limb plays an important role in metabolic improvement after duodenal-jejunal bypass in a rat model of diabetes.Surgery. 2016; 159: 1360-1371
- Mechanisms of diabetes improvement following bariatric/metabolic surgery.Diabetes Care. 2016; 39: 893-901
- Changing expression profiles of lncRNAs, mRNAs, circRNAs and miRNAs during osteoclastogenesis.Sci Rep. 2016; 6: 21499
- Genome-scale long noncoding RNA expression pattern in squamous cell lung cancer.Sci Rep. 2015; 5: 11671
- The dual targeting of EGFR and ErbB2 with the inhibitor Lapatinib corrects high glucose-induced apoptosis and vascular dysfunction by opposing multiple diabetes-induced signaling changes.J Drug Target. 2015; 23: 506-518
- Synergistic effects of metformin in combination with EGFR-TKI in the treatment of patients with advanced non-small cell lung cancer and type 2 diabetes.Cancer Lett. 2015; 369: 97-102
- Gastrointestinal hormones and polycystic ovary syndrome.Endocrine. 2014; 47: 668-678
- The intestinal immunoendocrine axis: novel cross-talk between enteroendocrine cells and the immune system during infection and inflammatory disease.Biochem Soc Trans. 2015; 43: 727-733
- Adiponectin, TNF-alpha and inflammatory cytokines and risk of type 2 diabetes: A systematic review and meta-analysis.Cytokine. 2016; 86: 100-109
- Diabetes mellitus risk factors in rheumatoid arthritis: a systematic review and meta-analysis.Clin Exp Rheumatol. 2015; 33: 115-121
- Adipokines, metabolic syndrome and rheumatic diseases.J Immunol Res. 2014; 2014: 1-14
- Mechanisms of surgical control of type 2 diabetes: GLP-1 is key factor.Surg Obes Relat Dis. 2016; 12: 1236-1242
- Interruption of the entero-pancreatic axis: effects of induced malabsorption.Eur J Clin Invest. 1990; 20: 58-64
- Responsive transporter genes within the murine intestinal-pancreatic axis form a basis of zinc homeostasis.Proc Natl Acad Sci U S A. 2004; 101: 14355-14360
- Long non-coding RNAs and human disease.Biochemical Society Transactions. 2012; 40: 902-906
Article info
Publication history
Published online: February 18, 2017
Accepted:
February 9,
2017
Received in revised form:
February 7,
2017
Received:
October 20,
2016
Identification
Copyright
© 2017 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.
